The stent is a medical device that is placed in blood vessel or other lumen in the body and that is used for dilation of its stricture or obstruction site and preservation of the lumen size and thus for treatment of various diseases caused by constriction or obstruction of blood vessel or other internal lumens. Examples of such stents include stents in the coiled shape of a single linear metal or polymeric material, those prepared by processing a metal tube with laser, assemblies of linear parts welded to each other with laser, those prepared by weaving multiple linear metal wires, and the like.
These stents are grouped into those expanded by balloon (balloon-expandable stents) and those expandable as they are when an external part restricting expansion is removed (self-expandable stents). Such a balloon-expandable stent is expanded and fixed to the lumen to be treated, as it is fixed to the balloon region of an intravascular catheter having an expandable part such as balloon at the distal end (balloon catheter) (in mounting step), the catheter fed to the site in the patient lumen to be treated, and the balloon expanded in the treatment site. Subsequently, the balloon is contracted, and the catheter withdrawn. In expanding the balloon, the expansion pressure is adjusted according to the condition of the lumen to be expanded and the mechanical strength of the stent used.
Demanded for such a stent are various properties such as strength sufficient for overcoming the pressure by the tubular organ to be expanded, flexibility allowing supply of the stent through a highly winding tubular organ to a desired site without problem, post-expansion flexibility preventing damage on the tubular organ during and after placement in tubular organ, evenness of expansion and fineness of design allowing uniform coverage of the tubular organ, and non-X ray permeability allowing the surgeon to identify the desired location during catheter placement operation by X ray monitoring. For the purpose of satisfying these requirements, various stent designs were proposed, as disclosed, for example, in Patent Documents 1 and 2.
Recently, these stents are used more frequently in angioplasty of heart and carotid artery, and, although it was shown that placement of such a stent was effective in reducing the frequency of restenosis statistically significantly, the frequency of restenosis still remains high even now. For example in the case of cardiac coronary artery, it was reported that stent placement resulted in restenosis at a frequency of approximately 20 to 30%. Restenosis is induced both by biological vascular damage and also by vascular damage due to stent placement. Typical vascular constriction-restenosis induced by vascular damage is considered to be caused by proliferation of the intimal smooth muscle cells. First, the vascular damage induces proliferation of the smooth muscle cells, and the proliferated smooth muscle cells migrate into the inner membrane. Subsequently, the smooth muscle cells in the inner membrane proliferate with substrate deposition, thickening the inner membrane.
For example, Patent Document 3 proposes application of an obstruction-preventing drug on stent for reduction of restenosis rate. Examples of the obstruction-preventing drugs discussed include anticoagulant agents, antiplatelet agents, anticonvulsant agents, antibacterial agents, anti-tumor drugs, antimicrobial agents, antiinflammatory agents, anti-metabolism agents, immunosuppressive agents, and the like. Also proposed was a method of reducing restenosis by coating on stent an immunosuppressive agent, such as cyclosporine, tacrolimus (FK-506), Sirolimus (rapamycin), mycophenolate mofetil, or the analogue thereof. Specifically for example, Patent Document 4 discloses a stent coated with an immunosuppressive agent Sirolimus (rapamycin), while, for example, Patent Document 5 discloses a stent coated with an anti-tumor drug taxol (paclitaxel). For example, Patent Documents 6 and 7 disclose stents coated with tacrolimus (FK-506). However, there is currently, still restenosis after stent placement occurring at a certain rate even when such a medicine-coated stent is used, and there is a need for optimization of the basic stent design for further reduction of the restenosis rate.
A property demanded for the stent is favorable evenness of expansion. A stent should always expand evenly and disperse and withstand the force from the body internal lumen. When a stent is expanded unevenly, local concentration of the load may cause problems such as breakage or fracture of the stent and damage of body organs caused by uneven contact therewith. These problems may exert a great influence on restenosis after stent placement. In the case of a drug-coated stent, it is important to make the stent release the drug evenly into the body, and thus, the uniformity in expansion of stent is even more important.
Normally, a stent is designed to have multiple repeated basic units and in this way to be expanded evenly. However, during actual use, the stent is often expanded unevenly, because of the bent of the body internal lumen site where the stent is placed, and thus, there is currently a need for a stent design allowing uniform expansion of the stent even at the bent site.
Also demanded for the stent is favorable flexibility. The stent is often left in a narrow bent blood vessel, and the flexibility of the stent is particularly important in such a case. When the stent is less flexible, large force is consistently applied thereto, for example, by heart beat in the vascular region of stent placement. Alternatively when the stent is flexible, it is possible to reduce the stimulus to the blood vessel to the lowest level. However, there is a limit in improving flexibility by reducing the number of links in the axial direction or by thinning the links. Reduction in the number of links leads to deterioration in uniformity in expanding the stent, while thinning of the links to increased concern about breakdown by metal fatigue and breakage of the link region.
Patent Document 1: Japanese Unexamined Patent Publication No. 2-174859
Patent Document 2: Japanese Unexamined Patent Publication No. 6-181993
Patent Document 3: Japanese Unexamined Patent Publication No. 5-502179
Patent Document 4: Japanese Unexamined Patent Publication No. 6-9390
Patent Document 5: Japanese Unexamined Patent Publication No. 9-503488
Patent Document 6: WO 02/065947
Patent Document 7: EP Patent No. 1254674